As therapeutic agents for diabetes mellitus, those which promote insulin secretion such as sulfonylurea agent and sulfonylamide agent, those which promote insulin resistance such as thiazolidione agent and biguanide agent, those which improve postcibal hyperglycemia such as α-glucosidase inhibitor, and the like have been known, and for the treatment of diabetes mellitus, these agents are used either solely or in combination.
Hydroxyproline widely occurs in nature as a major amino acid component of collagen and its N-acetyl derivative is used as an anti-inflammatory agent. It has also been used as a material for synthesis of various medicaments such as antibiotic substances of carbapenem type, blood pressure depressant, anti-asthma agent, improving agent for peripheral circulation and blood coagulation inhibitor. Further, due to its functional characteristic of having moisturizing property, it has been used for cosmetics as well (Bioscience and Industry, 1998, volume 56, no. 1, pages 11 to 16). It has also been used as a food additive for adjustment of quality of taste and improvement in taste of fruit juice, refreshing soft drink and commonly used food or as a material for flavor (“Commentary for Official Formulary of Food Additives”, Seventh Edition, published by Hirokawa Shoten, 1998, pages D-1114 to 1115).
With regard to a pharmacological action of hydroxyproline, an action for suppressing aging of the skin and an action for improving skin quality (WO 00/51561; Japanese Published Unexamined Patent Application No. 080321/2002), anti-inflammatory action, anti-rheumatic action, analgesic action and wound-healing action (Japanese Published Unexamined Patent Application No. 337526/1996) have been known, and there has been no report for an action for anti-diabetes mellitus and improving insulin resistance.
In addition, monohydroxylated amino acids have been known to have insulin-like action and/or insulin-sensitivity promoting action (Japanese Translation of PCT International Application No. 508435/2003) but no data concerning efficacy of hydroxyproline and hydroxyproline derivatives have been shown therein at all.